This is a renewal application for the Center for Drug Use and HIV Research. Our focus in this renewal will be From Discovery to Implementation and Back: Research Translation for the HIV/Substance (SU) Epidemic. Our current Center focused on interdisciplinary research related to HIV and substance use. During this period the Center experienced a growth in investigators (now located at 4 institutions) that provided new opportunities for synergy and collaboration, and investigators made many significant contributions to the field. However, HIV incidence, morbidity and mortality remain at unacceptably high rates, and substance use remains a critical barrier to reducing incidence and health disparities, accessing care, and maximizing the benefits of care. Substance users remain highly vulnerable and stigmatized, and a focus on the role of substance use in the epidemic is vital to our achieving the goals of the National HIV/AIDS Strategy (NHAS) (i.e., to reduce new infections, improve HIV-related health outcomes and reduce HIV-related health disparities). In addition, there is a need to expedite the research translation process (from discovery to public health impact) and to incorporate knowledge about the rapidly changing contexts that impact the epidemic, including biomedical advances and socio-economic changes. To create an infrastructure to address these challenges, we have made significant changes in our scope and Core structure for this renewal. The overarching aims of this Center renewal are to: (1) enhance the quality and impact of research to support the goals of the NHAS; (2) enhance projects' research translation efforts; and (3) enable projects to incorporate the study of the contextual changes influencing the HIV-substance use epidemic. We will achieve these aims through 6 Cores: an Administrative Core and 5 Research Support Cores: (1) Transdisciplinary Theoretical Synthesis and Development; (2) Infectious Diseases and Biomedical; (3) Transdisciplinary Research Methods; (4) Comparative Effectiveness Research; and (5) Pilot Projects and Mentoring. These Cores will work to enhance synergy and productivity across investigators, and stimulate the development of new initiatives, new investigators and new knowledge to impact the HIV-substance use epidemic.